Variant 9-69251016-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004817.4(TJP2):c.2992-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,608,104 control chromosomes in the GnomAD database, including 115,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12206 hom., cov: 32)

Exomes 𝑓: 0.37 ( 103320 hom. )

Consequence

TJP2
NM_004817.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.329

Variant links:

Genes affected

TJP2 (HGNC:11828): (tight junction protein 2) This gene encodes a zonula occluden that is a member of the membrane-associated guanylate kinase homolog family. The encoded protein functions as a component of the tight junction barrier in epithelial and endothelial cells and is necessary for proper assembly of tight junctions. Mutations in this gene have been identified in patients with hypercholanemia, and genomic duplication of a 270 kb region including this gene causes autosomal dominant deafness-51. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

TJP2 links:

ENSG00000285130 (HGNC:):

ENSG00000285130 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 9-69251016-G-A is Benign according to our data. Variant chr9-69251016-G-A is described in ClinVar as [Benign]. Clinvar id is 259554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4 linkuse as main transcript	c.2992-19G>A		intron_variant		ENST00000377245.9	NP_004808.2	Q9UDY2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9 linkuse as main transcript	c.2992-19G>A		intron_variant		1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 linkuse as main transcript	c.3379-19G>A		intron_variant				ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59819

AN:

151822

Hom.:

12185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.451

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.368

GnomAD3 exomes

AF:

0.359

AC:

89319

AN:

248978

Hom.:

17310

AF XY:

0.367

AC XY:

49604

AN XY:

135028

show subpopulations

Gnomad AFR exome

AF:

0.449

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.161

Gnomad SAS exome

AF:

0.423

Gnomad FIN exome

AF:

0.469

Gnomad NFE exome

AF:

0.384

Gnomad OTH exome

AF:

0.374

GnomAD4 exome

AF:

0.372

AC:

542207

AN:

1456164

Hom.:

103320

Cov.:

AF XY:

0.375

AC XY:

271942

AN XY:

724930

show subpopulations

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.211

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.216

Gnomad4 SAS exome

AF:

0.425

Gnomad4 FIN exome

AF:

0.467

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.394

AC:

59880

AN:

151940

Hom.:

12206

Cov.:

AF XY:

0.396

AC XY:

29404

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.452

Gnomad4 AMR

AF:

0.295

Gnomad4 ASJ

AF:

0.417

Gnomad4 EAS

AF:

0.176

Gnomad4 SAS

AF:

0.422

Gnomad4 FIN

AF:

0.456

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.369

Alfa

AF:

0.380

Hom.:

12699

Bravo

AF:

0.377

Asia WGS

AF:

0.335

AC:

1167

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cholestasis, progressive familial intrahepatic, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Hypercholanemia, familial 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.11

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over